Process of making oxymethylene-uric acid.



UNITED STATES PATENT OFFICE.

FRITZ ACH, OF MANNHEIM, GERMANY, ASSIGNOR TO 0. F. BOEHRINGER &

SOEl-INE, OF WALDl-IOF, GERMANY. I

PROCESS OF MAKING OXYMETHYLENE-URIC ACID.

SPEGIFICATTON forming part of Letters Patent No. 631,762, dated August 22, 1899.

Application filed April 16, 1898. Serial No. 677,856. ($pcoimens.)

To all whom it may concern.-

Be it known that I, FRITZ ACH, a citizen of the German Empire, residing at Mannheim, in the Empire of Germany, have invented certain new and useful Improvements in the Preparation of Alkylized Oxymethylene-Uric Acids; and I do hereby declare the following to be afull, clear, and exact description of the invention, such as will enable others skilled in the art to which it appertains to make and use the same.

This invention relates to the manufacture of those uric acids which are designated as oXymethylene-uric acidsthat is to say,

such uric acids in which a group or radical (ll-1 .011 replaces the H in one of the amido groups of the uric-acid molecule, one or more alkyl radicals being at the same time bound to one or several of the remaining nitrogen atoms.

The object of this invention is to use oxymethylene-uric acid and its alkyl derivatives, which have been set forth, together with their method of preparation, in an application by 2 5 myself and Lorenz Ach for Letters Patent of the United States, Serial No. 678,331, filed April 21, 1898, as starting materials for this purpose. As stated in said application, oxymethylene-uric acid and its alkyl derivatives on being heated with water, acids, or alkalies lose the formic aldehyde, combined with the corresponding uric acids, in their formation, the said uric acids being thereby regenerated.

Nevertheless I have succeeded in alkylizing 3 5 these oxymethylene-u ric acids by the employm ent of alkaline solutions in accordance with the methods set forth in German Patents Nos.

91,811 (including the Patents of Addition Nos. 92,310, 93,112, and 94,631) and 95,413

and in my Letters Patent of the United States Nos. 616,700, 616,656, 621,804, and 621,805.

Undersuch alkylizing methods the oxymethylene group (or formic aldehyde) is not split off and the alkylization proceeds according to 5 the following equation:

oo C-NCll Ol l-l-KOfl-l-haloid ether:

- oo C-NCH .O,I-I+haloid salt oo +H,o

AlkIN-C-NI-l while for the special case of methylation the 6 equation is as follows:

CH .N-ONH The alkyl-oxymethylene-uric acids so obtained are in part identical with the compounds prepared according tothe aforesaid application, Serial No. 67 8,331, filed April 21,

to conveniently obtain even such alkyl-uric such as, for example, 1-3-dimethyl-uric acid.

It is to be observed, moreover, that not only the series of oxymethylene-uric acids described in the aforesaid application Serial No. 678,331, filed April 21, 1898, may undergo further alkylization, but also t-he'oxymethylene-uric acid described by Tolleus in Ber'ichte der Deutschen Che-im'schen Gesellschaft, Vol. 30, page 2514, which contains more than one molecule of formaldehyde in one molecule of the uric acid.' This compound under the alkylizing process gives up a portion of its formic aldehyde, yielding as the final product 3-Inethyl-7-oxymethyleneuric acid.

To fully disclose my invention, I will now give a detailed description of the same as embodied in the following examples, which constitute What I consider the preferred manner of carrying the same into effect:

1. Preparation of -methyl-7-oxymethyZ-uric acicL-l dissolve fifteen parts of oxymethylene-uric acid in fifty parts, by volume, of double normal potash-lye or hydrate of potassium (corresponding to one and one-fourth molecules) and fifty parts of -water by the application of a gentle heat, (about 50, centigrade.) I then cool the solution to 15 cen tigrade or thereabout, and after cooling add thereto thirteen parts methyl iodid and heat the same to from to centigrade under pressuree. g., in an autoclave or digester. This temperatu reis maintained for two hours. After cooling a small quantity of colorless crystals will be found to have been thrown out, said crystals consisting for the greater part of 3-methyl-uric acid. The liquid is drained from these crystals by filtration, and the filtrate is allowed to stand or is evaporated in vacuo. After standing for some time or after evaporation the compound 3-methyl-7- oxyrnethylene-uric acid will have crystallized out of the solution. Its properties have been described in the aforesaid application Serial No. 678,331, filed April 21, 1898, and are as follows:

This new compound is readily soluble in boiling water, crystallizing therefrom in the form of colorless prisms, for the most part aggregated in druses or nodules. for a longer period formaldehyde escapes and 3-methyl-uric acid is regenerated. It possesses no melting-point, but is decomposed between 310 and 320 centigrade, this action being accompanied by darkeningand efiervescence or frothing. It gives the murexid test and reduces aminoniacal silver solutions even when gently heating.

3-methyl-oxymethylene-uric acid is readily soluble in dilute alkalies, including ammonia, and also in fuming hydrochloric acid. It has the formula O H N,,(), or

On boiling nN oo The starting p'roduct-oxymethylene-uric acid or '7 -0Xymethylene-uric acidand its method of production form the subject-matter of the aforesaid application Serial No. 678,331, filed April 21,1898. For the purposes of a full disclosure of the present invention the following description'of its preparation andproperties is now given:

Preparation of oxymethyZe-ne-uric acid. One part of uric acid proper is dissolved in fifteen parts of water, together with one part (corresponding to two and one-half molecules) of caustic potash of eighty per cent. strength, while gently warming. The solution is then allowed to cool to room temperature, and there are then added thereto 1.5 parts of concentrated solution of formic aldehyde. The whole is then allowed to stand at room temperature. After the lapse of several hours (for about twenty to twenty-five hours) the still clear solution is acidulated with HCl and treated with charcoal by shaking. After filtering the liquor the colorless filtrate is allowed to stand, when the oxymethylene-uric acid will be thrown out in the form of coarse shining prismatic crystals, which are then cleaned by washing with charcoal and ether and drying on the water-bath. The analysis of these crystals gives figures corresponding to the formula O H N O +II O or HNCO oo o-N.on,.on

oo+n,o.

HN-o-Nn The water of crystallization is slowly driven off by heating for a longer period at a temperature of from to centigrade.

The oXymethylene-uric acid, like uric acid proper, gives a strong murexid test with nitric acid or chlorin water and reduces ammoniacal silver solution in the cold.

The new product has no melting-point, but turns brown when heated beyond 320 centigrade and is decomposed at a still higher temperature, the decomposition being attended with darkening and frothing. It is readily recrystallized from water by boiling a short time after adding it thereto. It is thus obtained in the form of fine acicular crystals or short colorless prisms. On protracted boiling with water formaldehyde is split off and the uric acid proper regenerated.

Oxymethylene-uric acid is readily soluble 1mm... "W M l in dilute alkalies. Concentrated alkali lyes precipitate the corresponding salts after a short time in the form of colorless needles united to form globular aggregates.

The potassium salt of oxymethylene-uric acid may readily be obtained from crystallized acid urate of potassium if the latter is added to five times its weight of concentrated solution of formic aldehyde and the whole allowed to remain together for a considerable period of time-say about thirty to forty hoursthe whole being preferably shaken or agitated. The excess of formaldehyde solution is then removed by siphoning, decanting, or otherwise and then washing with alcohol. From the potassium salt so obtained the above-described oXymethylene-uric acid is obtained by super-saturating with mineral acids.

In preparing 3-methyl-'7-oxymethylene-uric acid it is not necessary to start with pure oXyniethylene-uric acid. An alkali urate, such as potassium urate, may be employed as the starting material, one part of such potas sium urate being heated under pressure (in a di gester or the like) to centigrade, together with 5.5 parts, by volume, of formaldehyde solution of forty-per-cent. strength and seven parts of water and 7.5 parts of methyl-iodid,

this temperature being maintained for about two hours while stirring'or agitating the mixture. The solution so obtained may then be used directly for preparing 3-methyl or 3-7-dimethyl uric acid, or it is further treated as above-that is to say, the 3-methyl-uric acid may be obtained from this solution by boiling with water, which causes the oxymethylene group or formic aldehyde to be split 0E, as set forth in the aforesaid application, Serial No. 678,331, filed April 21, 1898, (Case 0,) or the 3-7-dimethyl-uric acid may be obtained from this solution by reduction with hydrochloric acid in connection with tin by saturating the liquid with gaseous hydrochloric acid, adding thereto tin and completing the process by the method described in my application Serial No. 677,855, filed concurrently herewith, (Case P.)

II. Preparation of 1 -$-d imetltg Z-7-omymethy- Zane-uric acicL-Five parts of 3-methyl7-oxymethylene-uric acid whose mode of preparation has just been described or which may also be prepared as set forth in my application (Case 0) above referred to are dissolved in twenty-five parts, by volume,of double normal potash or potassium-hydrate lye and twentyi'ive parts, by volume, of water and 4.5 parts of methyl-iodid added, whereupon the whole is shaken until the latter completely disappears. After the lapse of about forty-eight hours the alkylization will be completed, an alkaline solution of the 1-3-dimethyl-7-oxymethylene-uric acid being obtained. From this alkaline solution the 1-3-dimethyl-7-oxymethylene-uric acid will be isolated by slightly acidulating the same and evaporating carefully. As set forth in the aforesaid application Serial No. 678,331, filed April 21, 1898, 1-3-dimethyl-uric acid may be obtained from this oxymethylene-uric acid by boiling with water, which causes the oxymethylene group or formic aldehyde to be split ofi.

From the above it will be seen that the generic feature of my present invention is the addition of a haloid ether, such as methyliodid, to an alkaline solution of a uric acid combined with formic aldehyde. Such uric acid maybe either uric acid proper or an alkyl derivative thereof, such as 3-methyl or 1-3- dimethyl uric acid. The uric acid may be combined with the formic aldehyde in the form of an oXymethylene-uric acid before the beginning of the process, or a urate may be added to formic aldehyde at the beginning of the process. Both of these forms are included under the generic term uric acid combined with formic aldehyde as employed above and in the claims. Itis also to be noted that one or several molecules of formic aldehyde may be combined with the uric acid.

WVhat I claim, and desire to secure by Letters Patent of the United States, is-

1. The process of preparing alkylized oxymetllylene-uric acids which consists in treating uric acid combined with formic aldehyde with a haloid ether.

2. The process of preparing alkylized oXymethylene-uric acids which consists in treating an alkaline solution of an oxymethyleneuric acid with a haloid ether.

3. The process of preparing alkylized oxymethylene-uric acids which consists in treating an alkaline solution of an oxymethylene uric acid with methyl-iodid.

at. The process of preparing alkylized oxymethylene-uric acids which consists in dissolving 7-oxymethylene-uric acid in potash lye and water and heating, then after cooling, adding to the solution methyl-iodid and heating under pressure, and agitation, all substantially inthe proportions and under the temperatures hereinabove given.

In testimony whereof I aflix my signature in presence of two witnesses.

FRITZ ACI-I.

\Vitnesses:

LORENZ AoH, GUSTAV HEINRICH. 

